Peptidomics of Cpe fat/fat mouse hypothalamus and striatum
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Chronic morphine administration is known to affect several neuropeptide systems, and this could contribute to the behavioral effects of opiates. To quantitate global changes in neuropeptide levels upon chronic morphine administration, we took advantage of a method that allows selective isolation of neuropeptides from brains of mice lacking carboxypeptidase E (Cpe fat/fat mice), a critical enzyme in the generation of many neuroendocrine peptides. We used a differential labeling procedure with stable isotopic tags and mass spectrometry to quantitate the relative changes in a number of hypothalamic and striatal peptides in Cpe fat/fat mice chronically treated with morphine. A total of 27 distinct peptides were detected in hypothalamus and striatum. Of these, 27 were identified by mass spectrometry-based sequencing, 1 was tentatively identified by the mass and charge, and 9 were not identified. The identified peptides included fragments of proenkephalin, prothyrotropin-releasing hormone, secretogranin II, chromogranin A and B, protachykinin B, provasopressin, promelanin concentrating hormone, and pro-SAAS. Upon morphine administration, although the levels of most of the peptides were unaltered (within a factor of 1.3 to 0.7 compared with saline control), the levels of a small number of peptides did show consistent changes (increased or decreased by 1.3-fold or more) in hypothalamus and/or striatum. Taken together, these results provide interesting insights into endogenous neuropeptide systems that are modulated by morphine and suggest further experiments to link candidate peptides with long-term effects of morphine.
- Bonci A., Bernardi G., Grillner P. and Mercuri N. B. (2003) The dopamine-containing neuron: maestro or simple musician in the orchestra of additition? Trends Pharmacol. Sci. 24, 172–177. CrossRef
- Che F. Y., Biswas R., and Fricker L. D. (2005a) Relative quantitation of peptides in wild-type and Cpe fat/fat mouse pituitary using stable isotopic tags and mass spectrometry. J. Mass. Spectrom. 40, 227–237. CrossRef
- Che F. Y. and Fricker L. D. (2002) Quantitation of neuropeptides in Cpe fat/fat mice using differential isotopic tags and mass spectrometry. Anal. Chem. 74, 3190–3198. CrossRef
- Che F.Y. and Fricker L. D. (2005) Quantitative peptidomics of mouse pituitary: comparison of different stable isotopic tags. J. Mass Spectrom. 40, 238–249. CrossRef
- Che F. Y., Yan L., Li H., Mzhavia N., Devi L. A., and Fricker L. D. (2001) Identification of peptides from brain and pituitary of Cpe fat/fat mice. Proc. Natl. Acad. Sci. U.S.A. 98, 9971–9976. CrossRef
- Che F. Y., Yuan Q., Kalinina E., and Fricker L. D. (2005b) Peptidomics of Cpe fat/fat mouse hypothalamus: effect of food deprivation and exercise on peptide levels. J. Biol. Chem. 280, 4451–4461. CrossRef
- Contet C., Kieffer B. L., and Befort K. (2004) Mu opioid receptor: a gateway to drug addition. Curr. Opin Neurobiol. 14, 370–378. CrossRef
- DiLeone R. J., Geoggescu D., and Nestler E. J. (2003) Lateral hypothalamic neuropeptides in reward and drug addiction. Life Sci. 73, 759–768. CrossRef
- Fricker L. D., Berman Y. L., Leiter E. H., and Devi L. A. (1996) Carboxypeptidase E activity is deficient in mice with the fat mutation. Effect on peptide processing. J. Biol. Chem. 271, 30,619–30,624.
- Fricker L. D., McKinzie A. A., Sun J., et al. (2000) Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing. J. Neurosci. 20, 639–648.
- Fukunaga Y. and Kishioka S. (2000) Enkephalinergic neurons in the periaqueductal gray and morphine withdrawal. Jpn. J. Pharmacol. 82, 175–180. CrossRef
- Georges F., Stinus L., Bloch B., and Le Moine C. (1999) Chronic morphine exposure and spontaneous with-drawal are associated with modifications of dopamine receptor and neuropeptide gene expression in the rat striatum. Eur. J. Neurosci. 11, 481–490. CrossRef
- Georgescu D., Zachariou V., Barrot M., et al. (2003) Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. J. Neurosci. 23, 3106–3111.
- Glowinski J. and Iversen L. L. (1966) Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopa in various regions of the brain. J. Neurochem. 13, 655–669. CrossRef
- Gudehithlu K. P. and Bhargava H. N. (1995) Modulation of preproenkephalin mRNA levels in brain regions and spinal cord of rats treated chronically with morphine. Peptides 16, 415–419. CrossRef
- Gygi S. P., Rist B., Gerber S. A., Tecek F., Gelb M. H., and Aebersold R. (1999) Quantitative analysis of complex protein mixtures using isotope-coded affinity tags. Nat. Biotechnol. 17, 994–999. CrossRef
- Harris G. C., Wimmer M., and Jones G. A. (2005) A role for lateral hypothalamic orexin neurons in reward seeking. Nature 437, 556–559. CrossRef
- Houshyar H., Manalo S., and Dallman M. F. (2004) Timedependent alterations in mRNA expression of brain neuropeptides regulating energy balance and hypothalmo-pituitary-adrenal activity after withdrawal from intermittent morphine treatment. J. Neurosci. 24, 9414–9424. CrossRef
- Laorden M. L., Milanes M. V., Angel E., Tankosic P., and Burlet A. (2003) Quantitative analysis of corticotropin-releasing factor and arginine vasopress in mRNA in the hypothalamus during chronic morphine treatment in rats: an in situ hybridization study. J. Neuroendocrinol. 15, 586–591. CrossRef
- Ludwig D. S., Tritos N. A., Mastaitis J. W., et al. (2001). Melanin-concentrating hormone overexpression in transgenic mice leads to obesity and insulin resistance. J. Clin. Invest. 107, 379–386. CrossRef
- Maldonado R., Blendy J. A., Tzavara E., et al. (1996) Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB. Science 273, 657–659. CrossRef
- Maldonado R., Negus S., and Koob G. F. (1992) Precipitation of morphine withdrawal syndrome in rats by administration of mu-, delta- and kappa-selective opioid antagonists. Neuropharmacology 31, 1231–1241. CrossRef
- Murtra P., Sheasby A. M., Hunt S. P., and De Felipe C. (2000) Rewarding effects of opiates are absent in mice lacking the receptor for substance P. Nature 405, 180–183. CrossRef
- Mzhavia N., Berman Y., Che F. Y., Fricker L. D., and Devi L. A. (2001) ProSAAS processing in mouse brain and pituitary. J. Biol. Chem. 276, 6207–6213. CrossRef
- Naggert J. K., Fricker L. D., Varlamov O., et al. (1995) Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Nat. Genet. 10, 135–142. CrossRef
- Nestler E. J. (2004) Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol. 25, 210–218. CrossRef
- Olive M. F. and Maidment N. T. (1998) Repeated heroin administration increases extracellular opioid peptide-like immunoreactivity in the blobus pallidus/ventral pallidum of freely moving rats. Psychopharmacology (Berl) 139, 251–254. CrossRef
- Robinson T. E. and Kolb B. (2004) Structural plasticity associated with exposure to drugs of abuse. Neuropharmacology 47 (Suppl 1), 33–46. CrossRef
- Saper C. B., Chou T. C., and Elmquist J. K. (2002) The need to feed: hoemostatic and hedonic control of eating. Neuron 36, 199–211. CrossRef
- Sayah M., Fortenberry Y., Cameron A., and Lindberg I. (2001) Tissue distribution and processing of proSAAS by proprotein convertases. J. Neurochem. 76, 1833–1841. CrossRef
- Shimada M., Tritos N. A., Lowell B. B., Flier J. S., and MaratosFlier E. (1998) Mice lacking melanin-concentrating hormone are hypophagic and lean. Nature 396, 670–674. CrossRef
- Skoubis P. D., Lam H. A., Shoblock J., Narayanan S., and Maidment N. T. (2005) Endogenous Enkephalins, not endorophins, modulate basal hedonic state in mice. Eur. J. Neurosci. 21, 1379–1384. CrossRef
- Trang T., Sutak M., Quirion R., and Jhamandas K. (2002) The role of spinal neuropeptides and prostaglandins in opioid physical dependence. Br. J. Pharmacol. 136, 37–48. CrossRef
- Van Bockstaele E. J., Peoples J., Menko A. S., McHugh K., and Drolet G. (2000) Decreases in endogenous opioid peptides in the rat medullo-coerulear pathway after chronic morphine treatment. J. Neurosci. 20, 8659–8666.
- Zachariou, V., Brunzell D. H., Hawes J., et al. (2003a) The neuropeptide galanin modulates behavioral and neurochemical signs of opiate withdrawal. Proc. Natl. Acad. Sci. U. S. A. 100, 9028–9033. CrossRef
- Zachariou V., Georgescu D., Sanchez N., et al. (2003b) Essential role for RGS9 in opiate action. Proc. Natl. Acad. Sci. U. S. A. 100, 13,656–13,661.
- Zhang R., Sioma C. S., Thompson R. A., Xiong L., and Regnier F. E. (2002) Controlling deuterium isotope effects in comparative proteomics, Anal. Chem. 74, 3662–3669. CrossRef
- Peptidomics of Cpe fat/fat mouse hypothalamus and striatum
Journal of Molecular Neuroscience
Volume 28, Issue 3 , pp 277-284
- Cover Date
- Print ISSN
- Online ISSN
- Humana Press
- Additional Links
- mass spectrometry
- drug addiction
- Industry Sectors